Ring-opening polymerization (ROP) of lactones and lactides is an addition polymerization reaction where the terminal end of a polymer acts as a reactive center and cyclic monomers join to form a larger polymer chain. In the case of a polylactide, an alkoxide of some metal having d-orbitals, like aluminum and tin, are considered to be good initiators for ROP of lactide (see, e.g., Biopolymers From Renewable Resources, Hartmann et al. (eds.), 1998, Spring-Verlag, Berlin, herein incorporated by reference in entirety). Stannous octoate or tin(II) bis-2-ethylhexanoic acid is the catalyst which has been researched most thoroughly and is generally used for bulk polymerization for lactide because of solubility in lactide, good reaction rate, high conversion, racemization of less than 1% and synthesis of higher molecular weight polymers (see, e.g., Du et al., Macromolecules (1995) 28(7):2124, herein incorporated in entirety).
Metal-free purely organic catalysts have been reported using either tertiary amines or phosphines as nucleophilic transesterification catalysts (see, e.g., Nederberg et al., Agnew Chem Int Ed (2001) 40:2712; Nederberg et al., Chem Comm (2001) 2006; Kamber et al., Chem Rev (2007) 107:5813, herein incorporated by reference in entirety.) A more recent class of organocatalysts for ROP are the N-heterocyclic carbenes (NHCs) which have been studied in the polymerization of ε-caprolactone to provide polycaprolactones with controlled molecular weight and low polydispersity (see, e.g., Kamber et al., Macromolecules (2009) 42(5): 1634, herein incorporated by reference in entirety.) All those processes rely on stringent anhydrous conditions and many involve reactions under pressure with solvent.
Polylactide may be copolymerized with a number of different monomers including other lactone monomers, such as, glycolide and caprolactone. Block copolymers of polycaprolactone and polylactide may be prepared in two ways: first, via a sequential addition of the required monomer on the living growing chain end of the first monomer; and second, by making a prepolymer with a hydroxyl end group to which the second monomer may be added in the presence of a catalyst (see, e.g., Bero et al., Polym Bull (1993) 21:9: Veld et al., J Polym Sci Part A Polym Chem (1997) 35:219, herein incorporated by reference in entirety).
The reactivity of lactone monomers is much lower than that of lactide monomers which generally proscribes one-pot processes. Thus, there remains a need to generate lactone/lactide-based copolymers in a single process format.